Acoustic, psychophysical, and neuroimaging measurements of the effectiveness of active cancellation during auditory functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) is one of the principal neuroimaging techniques for studying human audition, but it generates an intense background sound which hinders listening performance and confounds measures of the auditory response. This paper reports the perceptual effects of an active noise control (ANC) system that operates in the electromagnetically hostile and physically compact neuroimaging environment to provide significant noise reduction, without interfering with image quality. Cancellation was first evaluated at 600 Hz, corresponding to the dominant peak in the power spectrum of the background sound and at which cancellation is maximally effective. Microphone measurements at the ear demonstrated 35 dB of acoustic attenuation [from 93 to 58 dB sound pressure level (SPL)], while masked detection thresholds improved by 20 dB (from 74 to 54 dB SPL). Considerable perceptual benefits were also obtained across other frequencies, including those corresponding to dips in the spectrum of the background sound. Cancellation also improved the statistical detection of sound-related cortical activation, especially for sounds presented at low intensities. These results confirm that ANC offers substantial benefits for fMRI research

Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome.

The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, short limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional SRPS gene and further unravel the functional basis for IFT. We perform whole-exome sequencing and identify mutations in a new disease-producing gene, cytoplasmic dynein-2 light intermediate chain 1, DYNC2LI1, segregating with disease in three families. Using primary fibroblasts, we show that DYNC2LI1 is essential for dynein-2 complex stability and that mutations in DYNC2LI1 result in variable length, including hyperelongated, cilia, Hedgehog pathway impairment and ciliary IFT accumulations. The findings in this study expand our understanding of SRPS locus heterogeneity and demonstrate the importance of DYNC2LI1 in dynein-2 complex stability, cilium function, Hedgehog regulation and skeletogenesis

An electronic family health history tool to identify and manage patients at increased risk for colorectal cancer: protocol for a randomized controlled trial.

BackgroundColorectal cancer is the fourth most commonly diagnosed cancer in the United States. Approximately 3-10% of the population has an increased risk for colorectal cancer due to family history and warrants more frequent or intensive screening. Yet, < 50% of that high-risk population receives guideline-concordant care. Systematic collection of family health history and decision support may improve guideline-concordant screening for patients at increased risk of colorectal cancer. We seek to test the effectiveness of a web-based, systematic family health history collection tool and decision support platform (MeTree) to improve risk assessment and appropriate management of colorectal cancer risk among patients in the Department of Veterans Affairs primary care practices.MethodsIn this ongoing randomized controlled trial, primary care providers at the Durham Veterans Affairs Health Care System and the Madison VA Medical Center are randomized to immediate intervention or wait-list control. Veterans are eligible if assigned to enrolled providers, have an upcoming primary care appointment, and have no conditions that would place them at increased risk for colorectal cancer (such as personal history, adenomatous polyps, or inflammatory bowel disease). Those with a recent lower endoscopy (e.g. colonoscopy, sigmoidoscopy) are excluded. Immediate intervention patients put their family health history information into a web-based platform, MeTree, which provides both patient- and provider-facing decision support reports. Wait-list control patients access MeTree 12 months post-consent. The primary outcome is the risk-concordant colorectal cancer screening referral rate obtained via chart review. Secondary outcomes include patient completion of risk management recommendations (e.g. colonoscopy) and referral for genetic consultation. We will also conduct an economic analysis and an assessment of providers' experience with MeTree clinical decision support recommendations to inform future implementation efforts if the intervention is found to be effective.DiscussionThis trial will assess the feasibility and effectiveness of patient-collected family health history linked to decision support to promote risk-appropriate screening in a large healthcare system such as the Department of Veterans Affairs.Trial registrationClinicalTrials.gov, NCT02247336 . Registered on 25 September 2014

Renal impairment in a rural African antiretroviral programme

Background: There is little knowledge regarding the prevalence and nature of renal impairment in African populations initiating antiretroviral treatment, nor evidence to inform the most cost effective methods of screening for renal impairment. With the increasing availability of the potentially nephrotixic drug, tenofovir, such information is important for the planning of antiretroviral programmes Methods: (i) Retrospective review of the prevalence and risk factors for impaired renal function in 2189 individuals initiating antiretroviral treatment in a rural African setting between 2004 and 2007 (ii) A prospective study of 149 consecutive patients initiating antiretrovirals to assess the utility of urine analysis for the detection of impaired renal function. Severe renal and moderately impaired renal function were defined as an estimated GFR of ≤ 30 mls/min/1.73 m2 and 30–60 mls/min/1.73 m2 respectively. Logistic regression was used to determine odds ratio (OR) of significantly impaired renal function (combining severe and moderate impairment). Co-variates for analysis were age, sex and CD4 count at initiation. Results: (i) There was a low prevalence of severe renal impairment (29/2189, 1.3% 95% C.I. 0.8–1.8) whereas moderate renal impairment was more frequent (287/2189, 13.1% 95% C.I. 11.6–14.5) with many patients having advanced immunosuppression at treatment initiation (median CD4 120 cells/μl). In multivariable logistic regression age over 40 (aOR 4.65, 95% C.I. 3.54–6.1), male gender (aOR 1.89, 95% C.I. 1.39–2.56) and CD4<100 cells/ul (aOR 1.4, 95% C.I. 1.07–1.82) were associated with risk of significant renal impairment (ii) In 149 consecutive patients, urine analysis had poor sensitivity and specificity for detecting impaired renal function. Conclusion: In this rural African setting, significant renal impairment is uncommon in patients initiating antiretrovirals. Urine analysis alone may be inadequate for identification of those with impaired renal function where resources for biochemistry are limited

Abundance, Spatial Distribution, and Mortality of Young-of-the-Year Spotted Seatrout (Cynoscion nebulosus) Along the Gulf Coast of Florida

We used fixed-station and random-station sampling data from the period 1989-97 to examine spatial and temporal patterns in the abundance and size structure of young-of-the-year (YOY) spotted seatrout, Cynoscion nebulosus, in three Florida estuaries. YOY seatrout first appeared at shallow-water (\u3c1.5 m) seine sites in May-June in Choctawhatchee Bay (Florida Panhandle) and in April-May in Tampa Bay and Charlotte Harbor (both along the southwest Florida peninsula). Spotted seatrout were caught at deepwater (\u3e 1.6 m) trawl stations within 1-3 mo of their initial appearance at shallow-water sites. Most spotted seatrout were caught in waters \u3c3.7 m. Spring and summer peal\u27s in YOY abundance, corresponding to strong influxes of newly spawned individuals, were observed only in southwest peninsula estuaries. Depending on the estuary, the occurrence of YOY spotted seatrout at shallow-water sites was associated with some combination of seagrasses, mangroves, salinity, depth, temperature, and mud. Estimates of total instantaneous mortality rates for YOY spotted seatrout in Tampa Bay were 0.027·d-1 for fixed sites and to 0.025·d-1 for randomly selected sites

Equal Access and the Right to Marry

How should courts think about the right to marry? This is a question of principle, of course, but it has also become a matter of litigation strategy for advocates challenging different-sex marriage requirements across the country. We contend that courts and commentators have largely overlooked the strongest argument in support of a constitutional right to marry. In our view, the right to marry is best conceptualized as a matter of equal access to government support and recognition and the doctrinal vehicle that most closely matches the structure of the right can be found in the fundamental interest branch of equal protection law. Two other arguments have dominated litigation and adjudication so far, but both of them suffer from weaknesses. First, a liberty theory grounded in due process argues that everyone has a fundamental right to civil marriage. But civil marriage is a government program that states likely could abolish without constitutional difficulty. In that way, it differs from other family-related liberties such as the ability to procreate or engage in sexual intimacy. Second, an equality theory suggests that classifications on the basis of sexual orientation are constitutionally suspect. But that approach is unlikely to succeed in the Supreme Court or many state tribunals. Equal access, in contrast, requires states to justify laws that selectively interfere with civil marriage, regardless of any independent due process or classification-based equal protection violations. We show how this approach is grounded in precedent regarding intimate relationships, as well as in analogous law concerning voting and court access. Our proposal offers courts a workable way to evaluate the constitutionality of different-sex marriage requirements and a more satisfying conceptual basis for the right to marry generally. It also suggests a useful framework for thinking about recognition of other nontraditional family structures

Response to "The Legitimacy of Genetic Ancestry Tests"

Anthropolog

The Argument for Same-Sex Marriage (Debate)

Perry v. Schwarzenegger, in which a federal district court held California\u27s ban on same-sex marriages unconstitutional, is set for expedited review in the Ninth Circuit; many argue that the case will ultimately be decided by the Supreme Court. The arguments for and against the constitutionality of such statutes are thus at a fever pitch. In an article published earlier this year, Professors Nelson Tebbe and Deborah Widiss argued that marriage rights are best conceived of as an issue of equal access, rather than one of equal protection or substantive due process. Nelson Tebbe & Deborah A. Widiss, Equal Access and the Right to Many, 158 U. PA. L. REV. 1375, 1377 (2010). In The Argument for Same-Sex Marriage, Professors Tebbe and Widiss revisit the arguments they made in Equal Access and the Right to Mary and emphasize their belief that distinguishing between different-sex marriage and same-sex marriage is inappropriate. They lament the sustained emphasis on the equal-protection and substantive-due-process challenges in the Perry litigation and suggest that an equal-access approach is more likely to be successful on appeal. Professor Shannon Gilreath questions some of the fundamental premises for same-sex marriage in Arguing Against Arguing for Marriage. He challenges proponents to truly reflect on what there is to commend marriage to Gay people, and points to his own reversal on the question as evidence. Though he stands fully in opposition to critics of same-sex marriage who use the stance to veil attacks on equality generally, Gilreath argues that marriage can be seen as a further institutionalization of gays and lesbians that risks assimilationist erasure of Gay identity. Gilreath concludes by noting that to the extent that marriage is assumed to be normatively good, the Tebbe-Widiss equal access approach to same-sex marriage recognition may be the most successful; still, he invites those on all sides of the debate to vigorously challenge that assumption

The Argument for Same-Sex Marriage

Professors Tebbe and Widiss revisit the arguments they made in Equal Access and the Right to Marry and emphasize their belief that distinguishing between different-sex marriage and same-sex marriage is inappropriate. They lament the sustained emphasis on the equal-protection and substantive-due-process challenges in the Perry litigation and suggest that an equal-access approach is more likely to be successful on appeal. Professor Shannon Gilreath questions some of the fundamental premises for same-sex marriage. He challenges proponents to truly reflect on what there is to commend marriage to Gay people, and points to his own reversal on the question as evidence. Though he stands fully in opposition to critics of same-sex marriage who use the stance to veil attacks on equality generally, Gilreath argues that marriage can be seen as a further institutionalization of gays and lesbians that risks assimilationist erasure of Gay identity. Gilreath concludes by noting that to the extent that marriage is assumed to be normatively good, the Tebbe-Widiss equal access approach to same-sex marriage recognition may be the most successful; still, he invites those on all sides of the debate to vigorously challenge that assumption